Important roles of the lower urinary tract are urine storage and voiding, which are regulated by a coordinated action of the bladder and the urethra. That is, during urine storage, the bladder smooth muscle is relaxed and the urethral sphincter is contracted, whereby a state of high urethral resistance is maintained and urinary continence is thus maintained. On the other hand, during voiding, while the bladder smooth muscle is contracted, the urethral smooth muscle is relaxed, and contraction of the external urethral sphincter is also inhibited. Examples of disorders in the lower urinary tract include storage dysfunctions such as overactive bladder in which urine cannot be retained during urine storage and voiding dysfunctions in which urine cannot be drained sufficiently during voiding due to increase in the urethral resistance or decrease in the bladder contractile force. These two dysfunctions may develop simultaneously in some cases.
Voiding dysfunctions are caused by a decrease in the bladder contractile force or an increase in urethral resistance during voiding, and lead to voiding difficulty, straining during voiding, attenuation of the urinary stream, extension of voiding time, an increase in residual urine, a decrease in voiding efficiency, or the like. A decrease in the bladder contractile force during voiding is called underactive bladder, acontractile bladder, or the like. As a factor for decreasing the bladder contractile force during voiding, there are known increasing age, diabetes mellitus, benign prostatic hyperplasia, neurological diseases such as Parkinson's disease and multiple sclerosis, spinal cord injury, nerve damage caused by pelvic surgery, and the like (Reviews in Urology, 15: pp. 11-22 (2013)).
As a mechanism that induces bladder contraction during voiding, involvement of muscarinic receptor stimulation is known. In other words, the pelvic nerve that is a parasympathetic nerve innervating the bladder is excited during voiding, and acetylcholine is released from nerve terminals. The released acetylcholine binds to a muscarinic receptor in the bladder smooth muscle to cause contraction of the bladder smooth muscle (Journal of Pharmacological Sciences, 112: pp. 121-127 (2010)). The muscarinic receptors are currently divided into five subtypes, M1, M2, M3, M4, and M5, and it is known that a subtype involved in contraction of the bladder smooth muscle is mainly M3 (Pharmacological Reviews, 50: pp. 279-290 (1998), and The Journal of Neuroscience, 22: pp. 10627-10632 (2002)).
As a therapeutic agent for a decrease in the bladder contractile force during voiding, bethanechol chloride which is a non-selective muscarinic receptor agonist or distigmine bromide which is a choline esterase inhibitor is known. However, it is known that these drugs have cholinergic side effects, such as diarrhea, abdominal pain, and sweating. Further, cholinergic crisis is sometimes occurred as a serious side effect, therefore carefulness is required for the use (UBRETID (registered trademark) tablet 5 mg package insert, Torii Pharmaceutical Co., Ltd., Besacolin (registered trademark) powder 5% package insert, Eisai Co., Ltd.).
On the other hand, as a cause of an increase in urethral resistance, a voiding dysfunction associated with benign prostatic hyperplasia is well-known, which is characterized by partial obstruction of the urethra due to nodular hypertrophy of the prostate tissues. Adrenergic α1 receptor antagonists have now been used as therapeutic agents for the voiding dysfunction associated with benign prostatic hyperplasia (Pharmacology, 65: pp. 119-128 (2002)). On the other hand, the effectiveness of adrenergic α1 receptor antagonists on voiding dysfunctions not associated with benign prostatic hyperplasia is unclear, as compared with the voiding dysfunction associated with benign prostatic hyperplasia (Journal of Pharmacological Sciences, 112: pp. 121-127 (2010)).
Further, in voiding dysfunctions caused by a decrease in the bladder contractile force or an increase in the urethral resistance, residual urine after voiding may be observed in some cases. Increased residual urine may cause a decrease in effective bladder capacity, and thus cause overactive bladder symptoms such as urinary frequency, or severe symptoms, such as hydronephrosis, in some cases.
There is a demand for a therapeutic agent which is more effective on bladder or urinary tract diseases or symptoms thereof caused by a decrease in the bladder contractile force or an increase in the urethral resistance during voiding.
In Patent Document 1, it is described that a compound represented by the following general formula (A), including a compound of the following formula A1 disclosed in Example 315, has a Ba/F3 cell proliferative activity through a human c-myeloproliferative leukemia virus type P (c-Mpl) and has a thrombocyte increasing activity.

(in which R3 represents an aromatic hetero ring which may be substituted. For the other symbols, refer to the patent publication.)
In Patent Document 2, it is described that a compound represented by the following general formula (B), including a compound of the following formula B1 disclosed as the compound 38, has an activating effect on an AMPK pathway.

(in which a ring B represents a heteroarylene or the like, J represents —NR13C(O)— or the like, D1, D2, and D3 represent N, CH, or the like, and E represents —NR1R2 or the like. For the other symbols, refer to the patent publication.)